The purpose of the proposed project is to collect new information, not previoulsy known, about the sensitivity of hyperplastic nodules in the liver of ethionine-fed rats to acute and chronic effects of ethionine. The development of areas of hyperplasia and hyperplastic nodules is regarded as the most important precancerous step in hepatocarcinogenesis and apparently the hyperplastic nodules are resistant to some toxic effects of the carcinogen. Ethionine, a hepatic carcinogen, differs from the naturally occurring amino acid methionine only in the ethyl group. The resemblance of both compounds in chemical structure and in their metabolism gives a study of ethionine carcinogenesis a unique position among other carcinogens. Previous studies demonstrated a few distinct metabolic pathways of ethionine in vivo, which contribute to the toxic expression and to the detoxification of this substance. The metabolism of ethionine in hyperplastic nodules will be compared with that of the surrounding tissue of the same rat and of the normal liver tissue, with attempts to analyze the mechanism of the process of the selection of the hepatocytes as initial precursor cells from which a hepatocellular cancer could ultimately evolve.